BACKGROUND Immunotherapy is generally ineffective in patients with sarcomatoid renal cell carcinoma (RCC) and in patients with rapidly progressive metastatic or locally recurrent disease, with a median time to progression of approximately 2 months and a median survival of 4–7 months. Gemcitabine‐based regimens have modest antitumor activity, whereas doxorubicin is often used to treat sarcomatoid RCC. Based on the antitumor activity of doxorubicin and gemcitabine in collecting duct carcinoma of the kidney, the authors used this combination to treat selected patients with sarcomatoid or rapidly progressing RCC. METHODS Eighteen patients (11 males and 7 females; median age, 53 years; range, 31–81 years) with RCC (56% sarcomatoid; 44% other) were treated at 2 institutions in a collaborative study that was not institutional review board reviewed. Seven patients received previous treatment with interferon or interleukin‐2. Sites of metastases included the lung, soft tissue, bone, liver, and brain with 88% of patients having ≥ 3 sites of disease. Treatment consisted of doxorubicin (50 mg/m2) and gemcitabine (1500 or 2000 mg/m2) every 2–3 weeks with granulocyte–colony‐stimulating factor support. RESULTS A median of 5 courses was administered (range, 2–12 cycles). Therapy was well tolerated with no Grade 4 toxicities. Two patients had a complete response, five had a partial response, three had a mixed response, and one had stable disease. The median duration of response was 5 months (range, 2–21+ months). CONCLUSIONS These data suggested that the combination of doxorubicin and gemcitabine has antitumor activity in patients with sarcomatoid RCC or with rapidly progressing RCC. A prospective investigation of this combination in RCC is warranted. Cancer 2004. © 2004 American Cancer Society.

Anticipation is an earlier onset and/or increasing severity in successive generations. This study was conducted to determine whether anticipation occurs in families that exhibit both Hodgkin's (HD) and non-Hodgkin's (NHL) lymphoma in their pedigrees. Nine published reports of multi-generational lymphoma and 33 previously unreported families with both lymphomas were analysed for evidence of anticipation. The difference between age at onset for each affected related pair was tested against the null hypothesis that there is no difference in age at onset. Differences between disease-free survival in affected generations were determined. These analyses were also conducted separately using only parent -child pairs with an age of onset above 25 years in an effort to avoid ascertainment bias. Age at onset in studied cases was also compared with the HD and NHL series from the Surveillance Epidemiology and End Results (SEER) Program of the US National Cancer Institute. The mean age at onset in the child and parent generations of all case families (60.2 and 35.7 years, respectively) and in the selected pairs (61.5 and 45.6, years) were significantly different (mean difference 724.5 years; P 5 0.00001, and 715.9 years, P 5 0.00001, respectively). Mean anticipation for parents with HD and children with NHL was 76.8 years (P ¼ 0.01) for the unpublished and 714.4 years (P ¼ 0.002) for the published families (overall anticipation 710.1 years). Mean anticipation for parents with NHL and children with HD was 734.4 years (P 5 0.0001) for the unpublished and 732.7 years (P 5 0.0001) for the published families (overall anticipation 734.2 years, P 5 0.0001). The signed rank test rejected the null hypothesis which stated that there was no difference in age at onset between parents and children for overall, as well as selected pairs (P 5 0.00001). The null hypothesis was also rejected for both the parents with HD/children with NHL group and the parents with NHL/children with HD group pairs (P 5 0.0001). Age at onset distributions were significantly different for all generations with HD or NHL when compared to the SEER population (P 5 0.00001), except for the parents with NHL, which showed no difference. In addition, this study reports four previously unpublished families with three generations of lymphoma in their pedigrees. These data suggest that anticipation occurs in families that exhibit both HL and NHL and that both neoplasms may have a common genetic basis.

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